Acute Leukemia
Maram Haddad

Leukemia is a disease characterized by neoplastic proliferation of one of the blood-forming cells. The different types of leukemia are classified according to the cell type involved and as acute or chronic, depending on the state of maturity of the neoplastic cells and the expected duration of the disease. If left untreated all forms of leukemia are fatal; death is usually due to complications resulting from infiltration of the marrow by leukemic cells and replacement of normal hematopoietic cells. The average survival of untreated patients with acute leukemia is about three months, but the course of the disease may vary considerably. The are two major types of acute leukemia they are: acute lymphoblastic leukemia (ALL) and acute nonlymphoblastic leukemia. The nonlymphoblastic leukemias are often referred to more or less collectively as acute myelogenous leukemia (AML).

It is important to distinguish between the two major types because the response to chemotherapy is much more favorable in ALL than in AML and different drugs are ordinarily used for inducing remission. In ALL the lymphoblasts, characteristically have a high nuclear cytoplasmic ratio, the nuclei are not indented nor twisted, the number of nucleoli tends to be low (1 or 2), azurophilic granules are minimal and Auer rods are absent in the cytoplasm, promyelocytes and monocytes are uncommon, and, because they arise from normal precursors, the more mature cells of the granulocytic series appear normal. When leukemic blast are so primitive that they lack any signs of maturation, the designation acute undifferentiated leukemia (AUL) or stem-cell leukemia is often used. (Thorn, Adams, Braunworld, Isselbacher, Petersdorf, pg-1767.)

All types of leukemia are slightly more common in males than in females, however male predominance is less marked for acute leukemia (about 3:2) than for chronic lymphocytic leukemia (about 2:1) and the sex incidence is almost the same in very young children. Acute leukemia accounts for nearly half of all neoplasms in children. Patients with Down's syndrome or mongolism, a defect characterized by trisomy of chromosome 21, have approximately a twentyfold higher incidence of acute leukemia than normal. Both ALL and AML occur, and the type of leukemia appears to be related to that usually expected at the age of occurrence. A number of other congenital conditions are also associated with an increased incidence of leukemia, although the risk is less than in Down's syndrome. These include Fanconi's aplastic anemia; Blooms syndrome, ataxia-tel-angrectasia; Patau's syndrome, congenital sex-linked agammaglobulinemia; and Kostmann's agranulocytosis. Although there is no common specific chromosomal lesion, most of these syndromes are characterized either by chromosomal aneuploidy or by a tendency to chromosomal breakage. (Thorn, Adams, Braunworld, Isselbacher, Petersdorf, pgs-1768-1769.) Chromosome analysis of dividing leukemic cells in the marrow shows one or more karyotypic abnormalties in nearly half of patients with acute leukemia. When newer chromosome banding techniques are used, a high incidence of trisomy of chromosome 8 or 9 has been reported. People who develop acute leukemia often have a translocation that cuts chromosome 11 at a certain band in the long arm and places it on either chromosome 4 or 9. The translocation breakpoint on chromosome 11 occurs with in a intron of a gene. The breakpoint is called "ALU." An ALU sequence is a 300 base pair segment repeated about 500,000 times throughout the human genome. (R. Lewis, Wc Brown Publishers.) The Trithorax is a homeotic mutation, controlling segmentation and early embryogenesis. Wild type homeotic genes determine which developmental pathways a cell follows, this happens in fruit flies it is similar in humans with the leukemia cells in the following way, it encodes for a protein, leukemia arrests the normal process by which stem cells in the bone marrow give rise, through a series of developmental decisions, to several more specialized cell types. (R. Lewis, Wc Brown Publishers.) If there is translocation on chromosome 11 it might cause cancer if an oncogene is involved because if the oncogene is not working properly it can keep replicating which can cause it to become cancer. A mutation in an intron can affect the phenotype because it is caused by a frameshift mutation which can interpret a wrong sequence and therefore cause a mutation which can become cancerous. Familial leukemia is rare, but a few otherwise normal families have been reported in which multiple cases have occurred during one or more generations. Normal siblings and fraternal twins of leukemic children have a slightly higher risk of developing leukemia.

A number of drugs are used for treatment of leukemia and, now lies frequently than before chemotherapy was available, various forms of radiation. The therapeutic agents are all myelotoxic. Drugs with different modes of action are often combined, especially in the treatment of the acute leukemia ALL is more successfully treated than are other forms of acute leukemia: prolonged remissions and even cures can be brought about in children with the disease. Certain drugs are used to bring about remissions: if the remission is complete the patient becomes well, and no signs of the disease are demonstrable in the blood or bone marrow, drugs other than those used to induce remission often are more useful in maintaining the remission than the remmission - inducing drugs.


Thorn, Adams, Braunworld, Isselbacher, Petersdorf, Harrison's Principals of Internal Medicine-8th Edition-Chapter 324 pgs.1767 - 1777.

Ghozi, Berstein, Negreanu, Proceedings of the National Academy of Sciences of the United States 93: March 5, 1996-pgs. 1935 - 1940.

American Cancer Society Textbook of Clinical Oncology - 2nd edition 1995.

Clayman, Charles B., M.D. The American Medical Association Encyclopedia of Medicine. New York: Random House, 1989.

R. Lewis, Wc Brown Publishers, Case Workbook in Human Genetics-1994.

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